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13.1 Primary and secondary haemostasis and fibrinolysis interrelate to maintain blood fluidity, limit and arrest bleeding upon trauma, and remove blood clots when they are no longer needed.
13.2 Blood vessels have anticoagulant properties that prevent inappropriate clotting, and procoagulant mechanisms to promote clotting in response to trauma.
13.3 VWF binds platelets to exposed sub-endothelial collagen at the site of vascular injury via specific platelet receptors.
13.4 Platelets are tethered via VWF/GPIb interactions and then roll over to form more VWF/GPIb bridges. Stable adhesion occurs as a result of the involvement of additional platelet glycoprotein receptors.
13.5 Platelets become activated, release their granule contents, and aggregate.
13.6 Tissue factor is exposed upon vascular injury, which binds circulating FVIIa, the resultant complex activating FVII zymogen. FVIIa activates FX to fxa, which activates a small amount of FII to generate thrombin before the pathway is shut down by TFPI.
13.7 Platelets, FV, and FVIII. Only trace thrombin is generated due to the unavailability of FVa and the rapid intervention of TFPI.
13.8 Extrinsic tenase: FVIIa/TF/FX
Intrinsic tenase: FIXa/FVIIIa/FX
Prothrombinase: FXa/FVa/FII
All employ phospholipid and calcium ions as additional co-factors.
13.9 Platelets provide phospholipid for the multiprotein enzyme complexes and act as a physical platform. They also release or express crucial molecules. VWF protects FVIII from proteolytic degradation prior to involvement in secondary haemostasis.
13.10 Aa chains, Bb chains, and g chains.
13.11 Thrombin cleaves FPA and FPB from the Aa chains and Bb chains, respectively, of a fibrinogen molecule, resulting in the generation of a fibrin monomer. This exposes polymerization sites that join with complementary structures on the chains of other fibrin molecules to allow the formation of polymers.
13.12 To stabilize a fibrin clot by introducing covalent bonds between adjacent fibrin molecules.
13.13 Fibrinogen facilitates platelet aggregation in primary haemostasis and is the precursor of fibrin in secondary haemostasis.
13.14 a-AT is more involved in scavenger functions and b-AT mainly inhibits thrombin formed in the area of an injured vessel.
13.15 The activated forms of FV and FVIII (FVa and FVIIIa). (Note: You would lose marks in an exam if you answered just FV and FVIII.)
13.16 Thrombin is modified by thrombomodulin so that it loses its procoagulant properties and can then activate protein C. Protein C is anchored by EPCR which then positions the protein C for activation by the TM–thrombin complex. The activated protein C first dissociates from TM and then EPCR, where it anchors to the phospholipid surface of platelets with its cofactor protein S to inactivate FVa by peptide cleavage. Intact FV is required as an additional cofactor to perform the same action on FVIIIa.
13.17 FII, FVII, FIX, FX, protein C, protein S, protein Z.
13.18 Plasminogen attaches to the fibrin surface via lysine-binding sites on its kringles. The binding occurs in association with t-PA, which itself has minimal affinity for fibrinogen, so conversion of plasminogen to plasmin by t-PA is localized to the fibrin clot surface.
13.19 Cross-linking of a2-antiplasmin to the fibrin clot by FXIIIa retards fibrinolysis to prevent premature clot destruction. a2-antiplasmin interferes with the binding of Glu-plasminogen to fibrin and also forms inactive 1 : 1 complexes with plasmin. a2-macroglobulin backs up a2-antiplasmin in situations where the latter is swamped in plasma. TAFI removes lysine-binding sites from fibrin.
13.20 D-fragments of fibrinolysis are D-dimers as plasmin does not digest the cross-links between adjacent D-domains in a fibrin polymer. Fibrinogen lysis generates single D-fragments as the two D-domains within a fibrinogen molecule are not joined below the plasmin attack point.